Studies are being directed toward understanding the major histocompatibility complex, the structure and function of the products of this comples, and manipulations of immune responses to these products. Current studies include: 1) Characterization of major histocompatibility antigens: Congenic resistant strains of mice are developed, maintained, and used in serologic and immunochemical analyses of the MHC products of the mouse; 2) Studies of monoclonal antibodies to H-2 and Ia antigens: Hybridoma cell lines are produced by fusion of immune mouse spleen cells with mouse myeloma cells. The monoclonal anti-H-2- and anti-Ia antibodies produced by these hybridomas are analyzed by serologic and immunochemical means and are used to further characterize the fine structure of the MHC: 3) Characterization of receptor sites for histocompatibility antigens: Anti-idiotypic antisera are produced against anti-H-2 and anti-Ia hybridoma antibodies, and the effects of these antisera on in vitro and in vivo parameters of histocompatibility are assessed; and 4) Mechanism of tolerance to H-2 and Ia antigens: The humoral and cellular responses of radiation bone marrow chimers are examined, and the mechanism for maintenance of tolernace in these animals is studied. Mixed allogenic and xenogeneic chimeras, in which irradiated animals are reconstituted with mixtures of T-cell depleted donor and host marrow, are produced and the mechanism of tolerance and of immune responsiveness in these animals is studied in vivo and in vitro.